Structural Dynamics of the Magnesium-Bound Conformation of CorA in a Lipid Bilayer

SummaryThe transmembrane conformation of Thermotoga maritima CorA, a magnesium transport system, has been studied in its Mg2+-bound form by site-directed spin labeling and electron paramagnetic resonance spectroscopy. Probe mobility together with accessibility data were used to evaluate the overall dynamics and relative arrangement of individual transmembrane segments TM1 and TM2. TM1 extends toward the cytoplasmic side creating a water-filled cavity, while TM2 is located in the periphery of the oligomer, contacting the lipid bilayer. A structural model for the conserved extracellular loop was generated based on EPR data and MD simulations, in which residue E316 is located toward the five-fold symmetry axis in position to electrostatically influence divalent ion translocation. Electrostatic analysis of our model suggest that, in agreement with the crystal structure, Mg2+ -bound CorA is in a closed conformation. The present results suggest that long-range structural rearrangements are necessary to allow Mg2+ translocation.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (456 K)Download as PowerPoint slideHighlights► The conformation of Mg2+-bound CorA was evaluated using EPR spectroscopy ► We find overall structural correspondence with the recent crystal structures ► A model for the highly conserved extracellular loop was generated based on EPR data ► The loop might serve as an electrostatic sink and may participate in Mg2+ binding